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Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target.

Abstract：

BACKGROUND:Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts. METHODS:Tissue biopsies of healthy (n=9), ischemic (n=9) and hypertrophic (n=6) human hearts were analyzed by real time quantitative RT-PCR, confocal immunofluorescence and Western blot techniques. RESULTS:We found no expression of SGLT2 in either normal or pathological conditions, whereas SGLT1 was expressed in normal myocardial tissue and significantly upregulated in ischemia and hypertrophy, in association with increased phosphorylation in activating domains of the intracellular second messengers AMP-activated protein kinase (AMPK), extracellular-signal regulated kinase 1 and 2 (ERK-1/2) and mammalian target of rapamycin (mTOR). CONCLUSIONS:These findings open the possibility that hyperexpressed SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Di Franco A,Cantini G,Tani A,Coppini R,Zecchi-Orlandini S,Raimondi L,Luconi M,Mannucci E

doi

10.1016/j.ijcard.2017.05.032

subject

Has Abstract

pub_date

2017-09-15 00:00:00

pages

86-90

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(16)34166-3

journal_volume

243

pub_type

杂志文章

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